In this five-year project, laboratory analyses will be performed to characterize study subjects for known polymorphisms in genes regulating steroid metabolism, catecholestrogen formation, and detoxification of oxidative damage. Banked DNA samples from 441 ovarian cancer cases and 430 controls will be used to test the following hypotheses: 1) high-activity genotypes for the steroid metabolism genes CYP17 and EDH17B2 that increase concentrations of estrogen are associated with a greater risk of ovarian cancer; 2) high-activity genotypes for CYP1A1, CYP1B1, and MnSOD that increase contentrations of 4- hydroxylated catecholestrogens and oxidative stress, or low-activity genotypes for COMT and GST that decrease the detoxification of activated catecholestrogens, are positively associated with ovarian cancer risk; 3) high-activity genotypes for AhR and CYP1A2 that increase concentrations of 2-hydroxylated catecholestrogens are inversely associated with ovarian cancer risk. Dr. Anna Wu, the P.I. on the Los Angeles sub-contract during the first cycle of this grant, will assist with statistical analysis and the interpretation of results.